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Biological Trace Element Research Jul 2021It is known that cadmium induces damage to the testis. However, the significant cadmium impact on the testicular architecture and the mechanisms involved in this process...
It is known that cadmium induces damage to the testis. However, the significant cadmium impact on the testicular architecture and the mechanisms involved in this process are not clear. Besides, the relationship between dose, route, and time of exposure and injuries remains poorly understood. Thus, we aimed to assess whether cadmium exposure in any dose, route, and time of exposure causes significant alteration in the testicular tissue of murine models, as well as the main mechanisms involved. We performed a structured search on the Medline/PubMed and Scopus databases to retrieve studies published until September 2018. The results were organized into an Adverse Outcome Pathway (AOP) framework. Also, a bias analysis of included studies was performed. We included 37 studies, and most of them identified significant histopathologies in both tubule and intertubule regarding routes, in a dose- and time-dependent manner. The damages were observed after the first hours of exposure, mainly vascular damages suggesting that vasculature failure is the primary mechanism. The AOP showed that potential molecular initiating events may mimic and interfere with essential elements disrupting proteins (structural and antioxidants), change in the oxidative phosphorylation enzyme activities, and gene expression alteration, which lead to reproductive failure (adverse outcome). Analysis of methodological quality showed that the current evidence is at high risk of bias. Despite the high risk of bias, cadmium triggers significant lesions in the testis of murine models, regarding routes, in a dose- and time-dependent manner, mainly due to vascular changes. Therefore, cadmium is a risk factor for male reproductive health.
Topics: Animals; Antioxidants; Cadmium; Disease Models, Animal; Male; Mice; Testis
PubMed: 32951117
DOI: 10.1007/s12011-020-02389-0 -
Frontiers in Molecular Neuroscience 2021Alzheimer's disease (AD), a heterogeneous neurodegenerative disorder, is the most common cause of dementia accounting for an estimated 60-80% of cases. The pathogenesis...
Alzheimer's disease (AD), a heterogeneous neurodegenerative disorder, is the most common cause of dementia accounting for an estimated 60-80% of cases. The pathogenesis of AD remains unclear, and no curative treatment is available so far. Increasing evidence has revealed a vital role of non-coding RNAs (ncRNAs), especially long non-coding RNAs (lncRNAs), in AD. LncRNAs contribute to the pathogenesis of AD via modulating amyloid production, Tau hyperphosphorylation, mitochondrial dysfunction, oxidative stress, synaptic impairment and neuroinflammation. This review describes the biological functions and mechanisms of lncRNAs in AD, indicating that lncRNAs may provide potential therapeutic targets for the diagnosis and treatment of AD.
PubMed: 35095418
DOI: 10.3389/fnmol.2021.821002 -
Mini Reviews in Medicinal Chemistry 2023Neurodegenerative procedures include a large spectrum of disorders with diverse pathological features and clinical manifestations, such as Alzheimer's Disease (AD),...
BACKGROUND
Neurodegenerative procedures include a large spectrum of disorders with diverse pathological features and clinical manifestations, such as Alzheimer's Disease (AD), Parkinson's disease (PD), Multiple sclerosis, and Amyotrophic lateral sclerosis (ALS). Neurodegenerative diseases (NDs) are indicated by progressive loss of neurons and cognitive function, which is associated with free radical formation, extra and intercellular accumulation of misfolded proteins, oxidative stress, mitochondrial and neurotrophins dysfunction, bioenergetic impairment, inflammation, and apoptotic cell death. Boswellic acid is a pentacyclic triterpene molecule of plant origin that has been applied for treating several inflammatory disorders. Numerous studies have also investigated its' therapeutic potential against multiple NDs.
OBJECTIVE
In this article, we aim to review the neuroprotective effects of boswellic acid on NDs and the related mechanisms of action.
METHODS
The databases of PubMed, Google Scholar, Web of Sciences, and Scopus were searched to find studies that reported the effects of boswellic acid on NDs without time limits. Review articles, letters, editorials, unpublished data, and articles not published in the English language were not included in the study.
RESULTS
Overall, 17 studies were included in the present study (8 NDs in general, 5 AD, 3 PD, and 1 ALS). According to the reports, boswellic acid exerts anti-inflammatory, antioxidant, antiapoptotic, and neuromodulatory effects against NDs. Boswellic acid decreases Tau phosphorylation and amyloid-β (Aβ) generation in AD. This substance also protects nigrostriatal dopaminergic neurons and improves motor impairments in PD and modulates neurotransmitters, decreases the demyelination region, and improves behavioral functions in ALS.
CONCLUSION
Due to the significant effects of boswellic acid in NDs, more clinical studies are necessary to evaluate the pharmacokinetics of this substance because it seems that boswellic acid can be used as a complementary or alternative treatment in patients with NDs.
Topics: Humans; Neuroprotective Agents; Amyotrophic Lateral Sclerosis; Alzheimer Disease; Parkinson Disease
PubMed: 36998129
DOI: 10.2174/1389557523666230330113611 -
Marine Environmental Research Apr 2024Microplastics (5 mm - 1 μm) have become one of the major pollutants in the environment. Numerous studies have shown that microplastics can have negative impacts on... (Meta-Analysis)
Meta-Analysis Review
Microplastics (5 mm - 1 μm) have become one of the major pollutants in the environment. Numerous studies have shown that microplastics can have negative impacts on aquatic organisms, affecting their liver function levels. However, the extent of these effects and their potential toxicological mechanisms are largely unknown. In this study, a meta-analysis and systematic review were conducted to assess the effects of microplastics on fish liver function and summarize the potential toxicological mechanisms of microplastic-induced liver toxicity. The meta-analysis results indicate that compared to the control group, exposure to microplastics significantly affects fish liver indicators: aspartate aminotransferase (AST) (p < 0.001), alanine aminotransferase (ALT) (p < 0.001), alkaline phosphatase (ALP) (p < 0.001), total protein (TP) (p < 0.001), and lactate dehydrogenase (LDH) (p < 0.001), including oxidative stress indicators: superoxide dismutase (SOD) (p < 0.001), glutathione S-transferase (GST) (p < 0.001), glutathione (GSH) (p < 0.001), and malondialdehyde (MDA) (p < 0.001) in fish liver. For fish living in different environments, the potential toxicological mechanisms of microplastics exposure on fish liver may exhibit some differences. For freshwater fish, the mechanism may be that microplastics exposure causes overproduction of reactive oxygen species (ROS) in fish hepatocyte mitochondria. ROS promotes the expression of toll-like receptor 2 (TLR2) and activates downstream molecules myeloid differentiation factor 88 (MyD88) and tumor necrosis factor receptor-associated factor 6 (TRAF6) of the TLR2 signaling pathway, leading to phosphorylation of NF-κB p65. This leads to the release of inflammatory factors and oxidative stress and inflammation in fish liver. In addition, for seawater fish, the mechanism may be that microplastics exposure can cause damage or death of fish hepatocytes, leading to continuous pathological changes, inflammation, lipid and energy metabolism disorders, thereby causing significant changes in liver function indexes.
Topics: Animals; Microplastics; Plastics; Toll-Like Receptor 2; Reactive Oxygen Species; Liver; Oxidative Stress; Glutathione; Inflammation; Fishes
PubMed: 38442589
DOI: 10.1016/j.marenvres.2024.106423 -
Journal of the Neurological Sciences Sep 2019Among the organs/tissues affected in mitochondrial disorders (MIDs), the brain is the second most frequently affected. Cerebral imaging may correlate with clinical...
OBJECTIVES
Among the organs/tissues affected in mitochondrial disorders (MIDs), the brain is the second most frequently affected. Cerebral imaging may correlate with clinical findings but not necessarily. This review summarises and discusses current knowledge and recent advances concerning cerebral abnormalities on imaging in adult MIDs (≥18y).
METHODS
Systematic literature review.
RESULTS
The most common cerebral abnormalities in imaging in adult MIDs are, as in pediatric MIDs, white matter lesions, grey matter lesions, atrophy, optic atrophy, stroke-like lesions, calcifications, and ischemic stroke. Cerebral lesions may remain stable over years but some may undergo dynamic changes within shorter or longer period of times. Typical dynamic lesions are stroke-like lesions and grey matter lesions in the sense of progression or regression. Since cerebral lesions on imaging may or may not go along with clinical manifestations, it is crucial to screen all MID patients for cerebral involvement, which can be effectively accomplished by application of the MRI.
CONCLUSIONS
Cerebral imaging is of paramount importance for diagnosing and monitoring cerebral involvement in MIDs. Cerebral imaging in MIDs contributes to the understanding of the pathogenesis of cerebral involvement in MIDs.
Topics: Adult; Atrophy; Brain; Gray Matter; Humans; Magnetic Resonance Imaging; Mitochondrial Diseases; Neuroimaging; White Matter
PubMed: 31323519
DOI: 10.1016/j.jns.2019.07.013 -
Molecular Nutrition & Food Research Dec 2023Metabolic flexibility is essential for a healthy response to a high fat meal, and is assessed by measuring postprandial changes in blood markers including peripheral...
Systematic Review and Quantitative Data Synthesis of Peripheral Blood Mononuclear Cell Transcriptomics Reveals Consensus Gene Expression Changes in Response to a High Fat Meal.
SCOPE
Metabolic flexibility is essential for a healthy response to a high fat meal, and is assessed by measuring postprandial changes in blood markers including peripheral blood mononuclear cells (PBMCs; lymphocytes and monocytes). However, there is no clear consensus on postprandial gene expression and protein changes in these cells.
METHOD AND RESULTS
The study systematically reviews the literature reporting transcriptional and proteomic changes in PBMCs after consumption of a high fat meal. After re-analysis of the raw data to ensure equivalence between studies, ≈85 genes are significantly changed (defined as in the same direction in ≥3 studies) with about half involved in four processes: inflammation/oxidative stress, GTP metabolism, apoptosis, and lipid localization/transport. For meals consisting predominantly of unsaturated fatty acids (UFA), notable additional processes are phosphorylation and glucocorticoid response. For saturated fatty acids (SFA), genes related to migration/angiogenesis and platelet aggregation are also changed.
CONCLUSION
Despite differences in study design, common gene changes are identified in PBMCs following a high fat meal. These common genes and processes will facilitate definition of the postprandial transcriptome as part of the overall postcibalome, linking all molecules and processes that change in the blood after a meal.
Topics: Dietary Fats; Transcriptome; Leukocytes, Mononuclear; Consensus; Proteomics; Meals; Postprandial Period; Cross-Over Studies; Triglycerides
PubMed: 37817369
DOI: 10.1002/mnfr.202300512 -
International Journal of Molecular... Jun 2022Abundant experimental data suggest that hydrogen sulfide (HS) is related to the pathophysiology of Diabetes Mellitus (DM). Multiple molecular mechanisms, including... (Review)
Review
Abundant experimental data suggest that hydrogen sulfide (HS) is related to the pathophysiology of Diabetes Mellitus (DM). Multiple molecular mechanisms, including receptors, membrane ion channels, signalingmolecules, enzymes, and transcription factors, are known to be responsible for the HS biological actions; however, HS is not fully documented as a gaseous signaling molecule interfering with DM and vascular-linked pathology. In recent decades, multiple approaches regarding therapeutic exploitation of HS have been identified, either based on HS exogenous apport or on its modulated endogenous biosynthesis. This paper aims to synthesize and systematize, as comprehensively as possible, the recent literature-related data regarding the therapeutic/rehabilitative role of HS in DM. This review was conducted following the "Preferred reporting items for systematic reviews and meta-analyses" (PRISMA) methodology, interrogating five international medically renowned databases by specific keyword combinations/"syntaxes" used contextually, over the last five years (2017-2021). The respective search/filtered and selection methodology we applied has identified, in the first step, 212 articles. After deploying the next specific quest steps, 51 unique published papers qualified for minute analysis resulted. To these bibliographic resources obtained through the PRISMA methodology, in order to have the best available information coverage, we added 86 papers that were freely found by a direct internet search. Finally, we selected for a connected meta-analysis eight relevant reports that included 1237 human subjects elicited from clinical trial registration platforms. Numerous HS releasing/stimulating compounds have been produced, some being used in experimental models. However, very few of them were further advanced in clinical studies, indicating that the development of HS as a therapeutic agent is still at the beginning.
Topics: Diabetes Mellitus; Humans; Hydrogen Sulfide; Signal Transduction
PubMed: 35743160
DOI: 10.3390/ijms23126720 -
Current Pharmaceutical Design 2020Osteoarthritis (OA) is a leading cause of musculoskeletal disorders that mainly affects the elderly population. Some herbal medicines have the potential to alleviate the...
Osteoarthritis (OA) is a leading cause of musculoskeletal disorders that mainly affects the elderly population. Some herbal medicines have the potential to alleviate the pain associated with OA and improve physical activity mostly through anti-inflammatory and anti-oxidative properties. The aim of this study was to investigate the effects of herbal medicines, especially topical types, on osteoarthritis. In this systematic review, the keywords "osteoarthritis", "herbal compounds", "herbal medicine", "topical drug", "hydrogels", "cream" and "treatment" were used to search publications published from 2010 to 2019 and indexed in databases including PubMed, SCOPUS, Web of Science and Google Scholar. After screening of titles and abstracts and detection of duplicate publications, 38 eligible articles were included in the main review. We also included herbal formulations in vivo. Bioactive fractions of herbal medicines mostly worked on OA through suppression of interleukin-1β (IL-1β), inducing nuclear factor-κB (NF-κB) activation by inhibition of inhibitor of NF-κB (IκBα) phosphorylation, IκBα degradation, p65 phosphorylation, and p65 nuclear translocation, downregulation of NF-κB targets including COX-2 and MMPs, upregulation of collagen type II, cartilage-specific proteoglycans (CSPGs), β1-integrin, and expression of cartilage-specific transcription factor SOX-9 protein. Noticeably, herbal medicines do not produce desirable effects, thereby using their combinations with other therapeutic agents seem to exert substantial clinical outcomes. Herbal gels have demonstrated robustly significant healing effects on knee pain, stiffness and mobility. It is worth considering that because OA is a chronic disease, longer duration of the studies/trials would even lead to obtaining more reliable judgments regarding topical treatment tolerability, safety and efficacy and clarify local or systemic adverse effects. Stability and standardization of a defined amount or concentrations of herbal gels would give promising effects on OA treatment and pain relief.
Topics: Aged; Anti-Inflammatory Agents; Chondrocytes; Humans; NF-kappa B; Osteoarthritis; Signal Transduction
PubMed: 32348208
DOI: 10.2174/1381612826666200429013728 -
Heliyon Nov 2022Epithelial ovarian cancer (EOC) is a gynecologic malignancy with a poor prognosis due to resistance to first-line chemotherapeutic agents. Some cancer cells are...
Epithelial ovarian cancer (EOC) is a gynecologic malignancy with a poor prognosis due to resistance to first-line chemotherapeutic agents. Some cancer cells are primarily dependent on glycolysis, but others favor mitochondrial oxidative phosphorylation (OXPHOS) over glycolysis. Changes in metabolic reprogramming have been reported to be involved in cancer cell survival. In this review, we summarize the metabolic profiles (e.g., metabolic heterogeneity, plasticity, and reprogramming) and adaptation to the dynamic tumor microenvironment and discuss potential novel therapeutic strategies. A literature search was performed between January 2000 and March 2022 in the PubMed and Google Scholar databases using a combination of specific terms. Ovarian cancer cells, including cancer stem cells, depend on glycolysis, OXPHOS, or both for survival. Several environmental stresses, such as nutrient starvation or glucose deprivation, hypoxic stress, acidification, and excessive reactive oxygen species (ROS) generation, reprogram the metabolic pathways to adapt. The interaction between tumors and adjacent stromal cells allows cancer cells to enhance mitochondrial energy metabolism. The metabolic reprogramming varies depending on genomic and epigenetic alterations of metabolism-related genes and the metabolic environment. Developing accurate and non-invasive methods for early identification of metabolic alterations could facilitate optimal cancer diagnosis and treatment. Cancer metabolism research has entered an exciting era where novel strategies targeting metabolic profiling will become more innovative.
PubMed: 36406733
DOI: 10.1016/j.heliyon.2022.e11487 -
Metabolism: Clinical and Experimental Jan 2023We performed a meta-analysis to determine the changes induced by calorie restriction (CR) and bariatric surgery on human skeletal muscle mitochondria. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We performed a meta-analysis to determine the changes induced by calorie restriction (CR) and bariatric surgery on human skeletal muscle mitochondria.
METHODS
A systematic search of Medline and Web of Science was conducted. Controlled trials exploring CR (≥14 days) and mitochondrial function and/or content assessment were included. Moreover, studies analyzing weight loss following gastric surgery were included for comparison purposes. Human muscle data from 28 studies assessing CR (520 muscle samples) and from 10 studies assessing bariatric surgery (155 muscle samples) were analyzed in a random effect meta-analysis with three a priori chosen covariates.
MAIN RESULTS
We report a decrease (p < 0.05) (mean (95 % CI)) in maximal mitochondrial state 3 respiration in response to CR (-0.44 (-0.85, -0.03)) but not in response to surgery (-0.33 (-1.18, 0.52)). No changes in mitochondrial content were reported after CR (-0.05 (-0.12, 0.13)) or in response to surgery (0.23 (-0.05, 0.52)). Moreover, data from CR subjects showed a reduction in complex IV (CIV) activity (-0.29 (-0.56, -0.03)) but not in CIV content (-0.21 (-0.63, 0.22)). Similar results were obtained when the length of the protocol, the initial body mass index, and the estimated energy deficit were included in the model as covariates.
CONCLUSION
The observation of reduced maximal mitochondrial state 3, uncoupled respiration, and CIV activity without altering mitochondrial content suggests that, in human skeletal muscle, CR mainly modulates intrinsic mitochondrial function.
Topics: Humans; Caloric Restriction; Mitochondria, Muscle; Muscle, Skeletal; Bariatric Surgery; Mitochondria
PubMed: 36302454
DOI: 10.1016/j.metabol.2022.155336